Bile acids drive colonic secretion of glucagon-like-peptide 1 and peptide-YY in rodents

A large number of glucagon-like-peptide-1(GLP-1)- and peptide-YY (PYY)-producing L cells are located in the colon, but little is known about their contribution to whole body metabolism. Since bile acids (BAs) increase GLP-1 and PYY release, and since BAs spill over from the ileum to the colon, we decided to investigate the ability of BAs to stimulate colonic GLP-1 and PYY secretion. Using isolated perfused rat/mouse colon as well as stimulation of the rat colon in vivo. we demonstrate that BAs significantly enhance secretion of GLP-1 and PYY from the colon with average increases of 3.5- and 2.9-fold, respectively. Furthermore, we find that responses depend on BA absorption followed by basolateral activation of the BA-receptor Takeda-G protein-coupled-receptor 5. Surprisingly, the apical sodium-dependent BA transporter. which serves to absorb conjugated BAs, was not required for colonic conjugated BA absorption or conjugated BA-induced peptide secretion. In conclusion, we demonstrate that BAs represent a major physiological stimulus for colonic L-cell secretion. NEW & NOTEWORTHY By the use of isolated perfused rodent colon preparations we show that bile acids are potent and direct promoters of colonic glucagon-like-peptide 1 and peptide-YY secretion. The study provides convincing evidence that basolateral Takeda-G protein-coupled-receptor 5 activation is mediating the effects of bile acids in the colon and thus add to the existing literature described for L cells in the ileum.